RICTOR & RPS6KB1 Protein Protein Interaction Antibody Pair
- Known as:
- RICTOR & RPS6KB1 Protein Protein Interaction Antibody Pair
- Catalog number:
- DI0518
- Product Quantity:
- 1 Set
- Category:
- -
- Supplier:
- Abno
- Gene target:
- RICTOR & RPS6KB1 Protein Interaction Antibody Pair
Related genes to: RICTOR & RPS6KB1 Protein Protein Interaction Antibody Pair
- Gene:
- RICTOR NIH gene
- Name:
- RPTOR independent companion of MTOR complex 2
- Previous symbol:
- -
- Synonyms:
- MGC39830, AVO3, PIA, KIAA1999
- Chromosome:
- 5p13.1
- Locus Type:
- gene with protein product
- Date approved:
- 2009-05-29
- Date modifiied:
- 2019-03-19
- Gene:
- RPS6KB1 NIH gene
- Name:
- ribosomal protein S6 kinase B1
- Previous symbol:
- STK14A
- Synonyms:
- S6K1, p70(S6K)-alpha, PS6K, S6K
- Chromosome:
- 17q23.1
- Locus Type:
- gene with protein product
- Date approved:
- 1994-07-11
- Date modifiied:
- 2018-04-18
Related products to: RICTOR & RPS6KB1 Protein Protein Interaction Antibody Pair
Related articles to: RICTOR & RPS6KB1 Protein Protein Interaction Antibody Pair
- Macroautophagy/autophagy is a cellular catabolic process that results in lysosome-mediated recycling of organelles and protein aggregates, as well as the destruction of intracellular pathogens. Its role in the maintenance of the intestinal epithelium is of particular interest, as several autophagy-related genes have been associated with intestinal disease. Autophagy and its regulatory mechanisms are involved in both homeostasis and repair of the intestine, supporting intestinal barrier function in response to cellular stress through tight junction regulation and protection from cell death. Furthermore, a clear role has emerged for autophagy not only in secretory cells but also in intestinal stem cells, where it affects their metabolism, as well as their proliferative and regenerative capacity. Here, we review the physiological role of autophagy in the context of intestinal epithelial maintenance and how genetic mutations affecting autophagy contribute to the development of intestinal disease. AKT1S1: AKT1 substrate 1; AMBRA1: autophagy and beclin 1 regulator 1; AMPK: AMP-activated protein kinase; APC: APC regulator of WNT signaling pathway; ATF6: activating transcription factor 6; ATG: autophagy related; mice: mice with a specific deletion of in intestinal epithelial cells; ATP: adenosine triphosphate; BECN1: beclin 1; bsk/Jnk: basket; CADPR: cyclic ADP ribose; CALCOCO2: calcium binding and coiled-coil domain 2; CASP3: caspase 3; CD: Crohn disease; CDH1/E-cadherin: cadherin 1; CF: cystic fibrosis; CFTR: CF transmembrane conductance regulator; CGAS: cyclic GMP-AMP synthase; CLDN2: claudin 2; CoPEC: colibactin-producing ; CRC: colorectal cancer; CYP1A1: cytochrome P450 family 1 subfamily A member 1; DC: dendritic cell; DDIT3: DNA damage inducible transcript 3; DEPTOR: DEP domain containing MTOR interacting protein; DSS: dextran sulfate sodium; EGF: epidermal growth factor; EGFR: epidermal growth factor receptor; EIF2A: eukaryotic translation initiation factor 2A; EIF2AK3: eukaryotic translation initiation factor 2 alpha kinase 3; EIF2AK4/GCN2: eukaryotic translation initiation factor 2 alpha kinase 4; ER: endoplasmic reticulum; ERN1: endoplasmic reticulum to nucleus signaling 1; GABARAP: GABA type A receptor-associated protein; HMGB1: high mobility group box 1; HSPA5/GRP78: heat shock protein family A (Hsp70) member 5; IBD: inflammatory bowel disease; IEC: intestinal epithelial cell; IFN: interferon; IFNG/IFNγ:interferon gamma; IL: interleukin; IRGM: immunity related GTPase M; ISC: intestinal stem cell; LGR5: leucine rich repeat containing G protein-coupled receptor 5; LRRK2: leucine rich repeat kinase 2; MAP1LC3A/LC3: microtubule associated protein 1 light chain 3 alpha; MAPK/JNK: mitogen-activated protein kinase; MAPK14/p38 MAPK: mitogen-activated protein kinase 14; MAPKAP1: MAPK associated protein 1; MAVS: mitochondrial antiviral signaling protein; miRNA: microRNA; MLKL: mixed lineage kinase domain like pseudokinase; MLST8: MTOR associated protein, LST8 homolog; MNV: murine norovirus; MTOR: mechanistic target of rapamycin kinase; NBR1: NBR1 autophagy cargo receptor; NLRP: NLR family pyrin domain containing; NOD: nucleotide binding oligomerization domain containing; NRBF2: nuclear receptor binding factor 2; OPTN: optineurin; OXPHOS: oxidative phosphorylation; P: phosphorylation; Patj: PATJ crumbs cell polarity complex component; PE: phosphatidyl-ethanolamine; PI3K: phosphoinositide 3-kinase; PIK3C3/VPS34: phosphatidylinositol 3-kinase catalytic subunit type 3; PIK3R4: phosphoinositide-3-kinase regulatory subunit 4; PPARG: peroxisome proliferator activated receptor gamma; PRR5: proline rich 5; PRR5L: proline rich 5 like; PtdIns3K: phosphatidylinositol 3-kinase; PtdIns3P: phosphatidylinositol 3-phosphate; RB1CC1/FIP200: RB1 inducible coiled-coil 1; RER: rough endoplasmic reticulum; RHEB: Ras homolog, MTORC1 binding; RICTOR: RPTOR independent companion of MTOR complex 2; RIPK1: receptor interacting serine/threonine kinase 1; ROS: reactive oxygen species; RPTOR: regulatory associated protein of MTOR complex 1; RPS6KB1: ribosomal protein S6 kinase B1; SH3GLB1: SH3 domain containing GRB2 like, endophilin B1; SNP: single-nucleotide polymorphism; SQSTM1: sequestosome 1; STAT3: signal transducer and activator of transcription 3; STING1: stimulator of interferon response cGAMP interactor 1; TA: transit-amplifying; TFEB: transcription factor EB; TFE3: transcription factor binding to IGHM enhancer 3; TGM2: transglutaminase 2; TJ: tight junction; TJP1/ZO1: tight junction protein 1; TNBS: 2,4,6-trinitrobenzene sulfonic acid; TNF/TNFα: tumor necrosis factor; Tor: target of rapamycin; TRAF: TNF receptor associated factor; TRIM11: tripartite motif containing 11; TRP53: transformation related protein 53; TSC: TSC complex subunit; Ub: ubiquitin; UC: ulcerative colitis; ULK1: unc-51 like autophagy activating kinase 1; USO1/p115: USO1 vesicle transport factor; UVRAG: UV radiation resistance associated; WIPI: WD repeat domain, phosphoinositide interacting; WNT: WNT family member; XBP1: X-box binding protein 1; ZFYVE1/DFCP1: zinc finger FYVE-type containing 1. - Source: PubMed
Publication date: 2021/04/27
Foerster Elisabeth GMukherjee TapasCabral-Fernandes LilianeRocha Juliana D BGirardin Stephen EPhilpott Dana J - It is not clear whether inhibition of p70 ribosomal S6 kinase 1 (S6K1) is neuroprotective in cerebral ischemia-reperfusion. Decreasing blood-brain barrier (BBB) disruption has been associated with a better neuronal outcome in cerebral ischemia. We hypothesized that inhibition of S6K1 would decrease BBB disruption and infarct size in the early stage of cerebral ischemia-reperfusion. Middle cerebral artery occlusion (MCAO) was performed in rats under isoflurane anesthesia with controlled ventilation. 75 mg/kg of PF-4708671, an S6K1 inhibitor, was administered intraperitoneally 15 min after MCAO. After 1 h of MCAO and 2 h of reperfusion, the transfer coefficient (K) of C-α-aminoisobutyric acid and the volume of H-dextran distribution were determined to assess the degree of BBB disruption. At the same time point, phosphorylated Rictor (pT1135) and the infarct size were measured to evaluate S6K1 activity. In the PF-4708671 treated rats, the K of the ischemic-reperfused cortex was lower than the untreated rats (-22%, P < 0.05) and the volume of dextran distribution was significantly lower in most brain regions. With PF-4708671, a significant decrease in pT1135 Rictor was observed and the percentage of cortical infarct out of total cortical area was decreased (11.6 ± 2.0% vs 7.2 ± 1.1%, P < 0.0001). Our data demonstrate that PF-4708671 decreased the size of the cortical infarct in the ischemic-reperfused cortex with a decrease in BBB disruption suggesting that inhibition of S6K1 may induce neuronal survival in early cerebral ischemia-reperfusion and that a decrease of BBB disruption could be one of the contributing factors. - Source: PubMed
Publication date: 2019/05/04
Chi Oak ZKiss Geza KMellender Scott JLiu XiaLiu SharonJacinto EstelaWeiss Harvey R - Dyskinesia induced by L-DOPA administration (LID) is one of the most invalidating adverse effects of the gold standard treatment restoring dopamine transmission in Parkinson's disease (PD). However, LID manifestation in parkinsonian patients is variable and heterogeneous. Here, we performed a candidate genetic pathway analysis of the mTOR signaling cascade to elucidate a potential genetic contribution to LID susceptibility, since mTOR inhibition ameliorates LID in PD animal models. We screened 64 single nucleotide polymorphisms (SNPs) mapping to 57 genes of the mTOR pathway in a retrospective cohort of 401 PD cases treated with L-DOPA (70 PD with moderate/severe LID and 331 with no/mild LID). We performed classic allelic, genotypic, and epistatic analyses to evaluate the association of individual or combinations of SNPs with LID onset and with LID severity after initiation of L-DOPA treatment. As for the time to LID onset, we found significant associations with SNP rs1043098 in the EIF4EBP2 gene and also with an epistatic interaction involving EIF4EBP2 rs1043098, RICTOR rs2043112, and PRKCA rs4790904. For LID severity, we found significant association with HRAS rs12628 and PRKN rs1801582 and also with a four-loci epistatic combination involving RPS6KB1 rs1292034, HRAS rs12628, RPS6KA2 rs6456121, and FCHSD1 rs456998. These findings indicate that the mTOR pathway contributes genetically to LID susceptibility. Our study could help to identify the most susceptible PD patients to L-DOPA in order to prevent the appearance of early and/or severe LID in a future. This information could also be used to stratify PD patients in clinical trials in a more accurate way. - Source: PubMed
Publication date: 2018/07/10
Martín-Flores NúriaFernández-Santiago RubénAntonelli FrancesaCerquera CatalinaMoreno VerónicaMartí Maria JosepEzquerra MarioMalagelada Cristina - Schwann cell apoptosis is one of the characteristics of diabetic peripheral neuropathy (DPN). The mammalian target of rapamycin (mTOR) is a multifunctional signaling pathway that regulates cell apoptosis in various types of tissues and cells. To investigate whether the mTOR pathway is involved in cell apoptosis in the Schwann cells of DPN, diabetic mice and rat Schwann cells (RSC96) were chosen to detect phospho-mTOR (Ser 2448), phospho-S6K1 (Thr 389), phospho-4EBP1 (Thr 37/46), Bcl-2, Bax and cleaved caspase-3 by diverse pathological and biological techniques. The results showed that phospho-mTOR (Ser 2448) was decreased in the sciatic nerves of diabetic mice, concomitant with decreased Bcl-2, increased Bax, cleaved caspase-3 and cell apoptosis. In addition, high glucose treatment for 72 h caused a 35.95% decrease in the phospho-mTOR (Ser 2448)/mTOR ratio, a 65.50% decrease in the phospho-S6K1 (Thr 389)/S6K1 ratio, a 3.67-fold increase in the Bax/Bcl-2 ratio and a 1.47-fold increase in the cleaved caspase-3/caspase-3 ratio. Furthermore, mTORC1 inhibition, rather than mTORC2 inhibition, resulted in mitochondrial controlled apoptosis in RSC96 cells by silencing RAPTOR or RICTOR. Again, suppression of the mTORC1 pathway by a chemical inhibitor led to mitochondrial controlled apoptosis in cultured RSC96 cells in vitro. By contrast, activation of the mTORC1 pathway with MHY1485 prevented decreased phospho-S6K1 (Thr 389) levels caused by high glucose and cell apoptosis. Additionally, constitutive activation of S6K1 avoided high glucose-induced cell apoptosis in RSC96 cells. In summary, our findings suggest that activating mTORC1/S6K1 signaling in Schwann cells may be a promising strategy for the prevention and treatment of DPN. - Source: PubMed
Publication date: 2018/04/03
Zhu LinHao JunCheng MeijuanZhang CuihongHuo ChunxiuLiu YapingDu WeiZhang Xianghong - Cadmium (Cd), a toxic environmental contaminant, contributes to neurodegeneration. Rapamycin, a macrocyclic lactone, has shown preventive effect on Cd-induced neuronal cell death. However, the underlying mechanism is not fully understood. Here, we show that rapamycin prevented Cd-induced apoptotic cell death in neuronal cells. Coincidently, rapamycin markedly blocked Cd-induced phosphorylation of Akt, S6K1 and 4E-BP1 in the cells. Expression of a rapamycin-resistant and kinase-active mTOR (S2035T, mTOR-T), but not a rapamycin-resistant and kinase-dead mTOR (S2035T/D2357E, mTOR-TE), conferred resistance to rapamycin inhibition of Cd-induced cell death, implying that the preventive effect of rapamycin on Cd-induced neurotoxicity is mTOR kinase activity-dependent. It appeared that both mTORC1 and mTORC2 were involved in the inhibitory activity of rapamycin, as silencing raptor, rictor or raptor/rictor enhanced rapamycin's blockage of Cd-induced cell death. Furthermore, downregulation of S6K1, ectopic expression of constitutively hypophosphorylated 4E-BP1 or dominant negative Akt, or co-treatment with Akt inhibitor also potentiated the rapamycin's inhibitory effect. The findings indicate that rapamycin prevents Cd-induced neuronal cell death via suppressing both mTORC1 and mTORC2 pathways. Our results highlight that rapamycin may be exploited for the prevention of Cd-induced neurodegenerative disorders. - Source: PubMed
Publication date: 2015/05/19
Xu ChongLiu ChunxiaoLiu LeiZhang RuijieZhang HaiChen SujuanLuo YanChen LongHuang Shile